The study aimed to investigate the mediating role of job stress on relationship of job demand and work-life balance of nurses working in Multan, Pakistan. The study is based on the review of existing literature and collection of data through self-administered questionnaire. Sample was selected from nurses working within Multan by using convenience and snowball sampling techniques of non-probability sampling. This is a cross-sectional study as data is collected form the respondents at one specific point in time. A total of 134 questionnaires in English and Urdu were distributed in sample using convenience and snowball sampling and asked personally to fill the questionnaires; all the respondents returned the questionnaires. The results showed that most of the nurses working in Multan are young, single and well-qualified. All the three variables are positively correlated to each other. The mediation model presented by Baron and Kenny (1986) is applied and tested by hierarchical regression analysis. The mediation is checked by two models: in model no.1 job demand predicted work-life balance and in model no.2 both job demand and job stress predicted work-life balance. The regression analysis showed that both job demand and job stress brought change in work-life balance and increase of 19.9% is noticed in model no.2 after addition of job stress. As hypothesized, the job demand though affects the work-life balance of nurses but when the job becomes more demanding it creates job stress which more adversely affects the work-life balance of nurses. The results are applicable to the nurses working in Multan. Future research may further study the issue by enhancing the sample size and by adding other variables such as ?staff morale? and ?workplace environment?. The practical suggestions include implementation of results to reduce the level of stress in nurses and improve their existing conditions.